Major emphasis will be placed on the experimental neuropathy induced in rats by p-bromophenylacetylurea (BPAU). The extended time course of distal turnaround and retrograde transport of 35S-methionine labeled protein will be followed in both sensory and motor nerves. The results will be used to test the hypothesis that BPAU-neuropathy results directly form an impairment in the switching of mateial from anterograde to retrograde transport. Electron-microscopy and light microscope-autoradiography will also be used to determine whether the early stage of BPAU-neuropathy involves an increased local retention of transported material in nverve terminals and distal axons. The effect of BPAU on energy metabolism will be investigated. Non-toxic analogues of BPAU will be tested to determine whether the effects of BPAU on retrograde transport are specific. The uptake and half-life of 14CBPAU in nervous tissue will be investigated. A long-term objective is a mechanistic understanding of an experimental neuropathy that can be regarded as a model for human peripheral nerve disease.